Protein Voyeurism Could Help Save Lives

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A high-throughput method reveals where over 100 small molecules bind to the protein PTP1B. A select few of these binding areas can send signals to the active site (red) to control PTP1B's activity (via Advanced Science Research Center, GC/CUNY)

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Understanding how the body (and all of its moving parts) works is key to treating and curing disease.

A fundamental element of that process is comprehending proteins—sophisticated structures that perform specific jobs to keep us functioning and healthy.

These tiny machines are turned on or off via a two-step process, by which one part of the protein signals another part to start or stop its job. If this procedure, called allostery, gets disrupted, chaos ensues.

Scientists at the Advanced Science Research Center (ASRC) at The Graduate Center, CUNY, however, have designed a method for getting inside the proverbial mind of proteins to see what makes them tick.

“Just like it’s hard to guess how a light switch is wired to a light bulb in a room without seeing behind the walls, it’s hard to predict what remote areas of a protein are wired to its active site without seeing the details inside the structure,” according to Daniel Keedy, assistant professor with the ASRC’s Structural Biology Initiative and with The City College of New York’s chemistry and biochemistry departments.

Using X-ray crystallography, the team was able to see how atoms move inside the protein—gliding like windshield wipers or Newton’s cradle toy to send messages.

Further experiments determined which small molecules bind to these signaling sites.

“This two-step process allows us to see not only where the signaling originates inside PTP1B, but also what small molecules are capable of sending messages to the active site,” Keedy said in a statement. “This knowledge could one day help us develop therapies that send specific messages to control a protein’s activity and disrupt the development of type 2 diabetes.”

Keedy and his colleagues have so far looked only at PTP1B. But their method could be applied to other proteins in the human body, potentially helping to develop new drug therapies, and ultimately save lives.